Regulating Inducible Transcription Through Controlled Localization

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Science's STKE  17 May 2005:
Vol. 2005, Issue 284, pp. re6
DOI: 10.1126/stke.2842005re6

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Inducible transcription factors are key targets of many signaling pathways. Transcription of target genes by inducible transcription factors is regulated by numerous mechanisms that affect access to and affinity for target genes, interaction with coactivators, or transcriptional activity itself. Because of cytoplasmic sequestration, a subset of transcription factors are maintained inactive in unstimulated cells until the proper inducing stimulus is provided. The mechanism of cytoplasmic sequestration was originally thought to involve the masking of nuclear localization signals (NLSs) on transcription factors. However, recent reports suggest that such a static model of cytoplasmic retention is perhaps far too simple, and that these inducible transcription factors instead constantly shuttle between the cytoplasm and the nucleus. Furthermore, it has been shown that the sequestration of inducible transcription factors can be accomplished through multiple mechanisms in addition to masking of the NLSs. In this review, we discuss a few signaling pathways that illustrate mechanisms of controlling the localization of inducible transcription factors and provide a more encompassing model to explain how inducible transcription factors may be regulated by cytoplasmic sequestration.